Glioma
Conditions
Keywords
glioma, photon therapy, proton therapy, neurocognitive function
Brief summary
Patients with grade 2 and 3 gliomas who received photon radiation therapy as part of their standard treatment are at risk of developing cognitive impairments, depending on the tumor's location and the size of the target volume. The extent to which these are caused in individual cases by the brain tissue within the target volume, which is necessarily exposed to a high dose, or whether they can be modified by differences in the exposure of surrounding brain regions exposed to low or moderate doses, is unknown. With the help of proton therapy, the risk of neurocognitive dysfunction could potentially be reduced by decreasing the brain volumes outside the target volume that are exposed to radiation therapy and receive a low dose. Based on current knowledge of relative biological effectiveness, the efficacy of proton therapy on the tumor compared to photon therapy can be considered equivalent with lower levels of uncertainty. In the present study, the impact of photon irradiation versus proton irradiation on neurocognition will now be directly compared. A bicentric, randomized study will investigate whether treating patients with WHO Grade 2 and 3 gliomas with proton radiation results in a different temporal course of neurocognitive function after treatment compared to photon radiation therapy.
Interventions
RADIATIONProton therapy
Grade 2 gliomas: 5 × 1.8 GyRBE to a total of 54 GyRBE Grade 3 gliomas: 5 × 1.8 GyRBE to a total of 59.4 GyRBE (with concurrent chemotherapy) or 5 × 2.0 GyRBE to a total of 60 GyRBE
RADIATIONPhoton therapy
Grade 2 gliomas: 5 × 1.8 GyRBE to a total of 54 GyRBE Grade 3 gliomas: 5 × 1.8 GyRBE to a total of 59.4 GyRBE (with concurrent chemotherapy) or 5 × 2.0 GyRBE to a total of 60 GyRBE
Sponsors
University Hospital, Essen
University Hospital Giessen and Marburg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
randomized in two arms: Proton vs. photon therapy. Chemotherapy according to local standard (sequential temozolomide or procarbazine/CCNU).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Histologically confirmed IDH-mutated WHO Grade 2 or 3 glioma with an indication for radiation therapy as determined by the local tumorboard at the study center * 2\. Tumor classification according to the 2021 WHO Classification, including the presence of the following markers: * IDH1/2 mutation * ATRX and/or 1p19q codeletion status * CDKN2A/B codeletion status * 3\. A Karnofsky Performance Status of ≥ 70% * 4\. Patients must be ≥ 18 years of age * 5\. Radiation therapy must begin within 7 weeks of surgery in patients with CNS WHO Grade 2 IDH-mutated gliomas. In individual cases, the start may be delayed, but not later than 10 weeks after surgery * 6\. For patients with WHO Grade 2 IDH-mutated CNS gliomas, the following applies: * There is an indication for radiation therapy (partial tumor resection, age \> 40 years, relevant neurological deficit) * Enrollment in the study at the time of tumor progression is possible, even without a time constraint relative to the initial surgery, if the following criteria are met: * There was initially no indication for radiation therapy * At the time of tumor progression, there is an indication for radiation therapy as determined by the local tumor board * At the time of recurrence, no repeat surgery is required to confirm the diagnosis if there is no imaging evidence of malignancy (see exclusion criterion No. 4) * Radiation therapy must begin within 7 weeks after the recurrence MRI (or surgery, if a repeat surgery has been performed). In individual cases, treatment may begin later, but no later than 10 weeks after the recurrence MRI/surgery * 7\. For patients with WHO Grade 3 IDH-mutated CNS gliomas, radiation therapy must begin within 7 weeks after surgery . In individual cases, treatment may begin later, but no later than 10 weeks after surgery * 8\. At the time of study enrollment, the interval since the last surgery should be ≥ 2 weeks. Patients must have recovered from the effects of the surgery * 9\. The patient must consent and be able to undergo a neurocognitive baseline assessment prior to administration of the first radiation dose * 10\. The patient must provide written informed consent to participate in the study prior to enrollment * 11\. The study participant must be able to understand the purpose and implications of the study and must be willing to follow the clinical study instructions and, as far as can be anticipated, attend all scheduled study visits. * 12\. Women of childbearing potential must have a negative pregnancy test (serum or urine) that is no older than 7 days at the time of the first study intervention. * 13\. Laboratory values not older than 3 weeks prior to study enrollment: Absolute neutrophil count ≥ 1,500/mm³, Platelet count ≥ 100,000/mm³, Hemoglobin (Hb) level \> 10 g/dL, Total bilirubin level ≤ 1.5 times the upper limit of normal, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 3 times the upper limit of normal, Creatinine level ≤ 1.5 times the upper limit of normal *
Exclusion criteria
Patients who meet any of the following criteria will not be enrolled in the study. General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognition | three years after finishing radiotherapy | Composite Z-Score (Neurocognition) based on the cognitive domains assessed 3 years after completion of radiation therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognition | 4 weeks and 1, 2, 4, 5, and 6 years after completion of radiation therapy | Composite Z-Score (neurocognition) based on the assessed cognitive domains (see footnote: study protocol) at 4 weeks and 1, 2, 4, 5, and 6 years after completion of radiation therapy |
| Decline of cognitive domains | At 4 weeks and 1, 2, 3, 4, 5, and 6 years after completion of radiation therapy | A decline of \> 1 SD from the baseline score in one of the cognitive domains studied when compared to the baseline assessment at 4 weeks and 1, 2, 3, 4, 5, and 6 years after completion of radiation therapy |
| Quality of Life | Pre radiation until 6 years after finishing radiotherapy | Quality of Life According to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30; Version 3.0; Part A with 28 questions on a Likert scale, 28 to 112 points, Higher score means lower quality of life; Part B with 2 questions on a Likert scale, 2 to 14 points, Lower score means lower quality of life ) |
| Overall survival | From tumor diagnosis to death (usually 24 to 120 months) | — |
| Progression free survival | From date of first surgery until the date of first progression (MRI) | PFS |
| Adverse events | From pre radiation until progression or 3 years after completion of radiation therapy (whichever comes first) | Incidence of Grade III-V adverse events according to CTCAE V5.0 up to the primary endpoint (3 years after completion of radiation therapy) or until disease progression |
| Perilesional brain tissue changes | At 4 weeks, 1, 2, 3, 4, 5, and 6 years after completion of radiation therapy | Frequency of perilesional brain tissue changes on follow-up MRI, classified by severity (Grades 1-4 (as defined by Fouladi 2004) at 4 weeks, 1, 2, 3, 4, 5, and 6 years after completion of radiation therapy |
Countries
Germany
Contacts
CONTACTSied Kebir, PD Dr med.
CONTACTChristoph Oster, Dr. med.
Outcome results
None listed